Extrahepatic Replication and Genomic Signatures of the Hepatitis E Virus in the Kidney

作者：Avista Wahid, Nele Meyer, Christine Wundes, Lucas Hüffner, Saskia Janshoff, Nicola Frericks, Martina Friesland, Katja Dinkelborg, Elmira Aliabadi, Fenja Laue, Markus Cornberg, Benjamin Maasoumy, Birgit Bremer, Sven Pischke, Tobias Mueller, Julian zur Schulze Wiesch, Julia Benckert, Rainer G. Ulrich, Svenja Hardtke, Petra Dörge, Florian W. R. Vondran, Ansgar W. Lohse, Michael P. Manns, Daniel Tödt, Heiner Wedemeyer, Thomas Pietschmann, Eike Steinmann, André Gömer, Patrick Behrendt · 发表于：Liver International · 年份：2025 · DOI：10.1111/liv.70183 · 被引用次数：7 · 研究领域：Hepatitis Viruses Studies and Epidemiology、Hepatitis B Virus Studies、Viral gastroenteritis research and epidemiology

INTRODUCTION: The hepatitis E virus (HEV; species Paslahepevirus balayani) is a common human pathogenic and zoonotic virus that can cause both acute fulminant and chronic hepatitis. Despite its reputation as a hepatotropic virus, HEV infection is also associated with a number of extrahepatic diseases, including kidney disorders. However, the extent to which HEV replicates in kidney cells remains unclear. The present study aims to investigate the capacity of HEV to propagate in kidney cells in vitro and to assess whether HEV displays mutational signatures that correlate with compartmentalisation in vivo. METHODS: We use HEV cell culture models to study the replication cycle and the effect of antivirals in human kidney cell lines and primary cells. In addition, we identified patients with chronic HEV infection (n = 9) from which we then sequenced the viral RNA of urine, stools and plasma to analyse the viral sequence composition, to assess intra-host diversity and compartmentalisation (n = 2). RESULTS: A wide range of human kidney cell lines as well as primary cells supports viral entry, replication and propagation of HEV in vitro. Interestingly, the broad-spectrum antiviral ribavirin was less effective in inhibiting HEV replication in some kidney cells. Sequencing of HEV RNA-directed RNA polymerase coding region from plasma, stool and urine and subsequent phylogenetic analysis revealed diversification of HEV into tissue-specific viral subpopulations. In particular, the viruses...